This proposal represents the Mayo Heart Failure Program's application to participate in the Heart Failure (HF) Clinical Research Network (HF-CRN) whose goal is to accelerate research in the diagnosis and management of HF in order to improve outcomes through evaluation of novel therapeutic strategies. In this application, we document our qualifications to participate in the HF-CRN and our willingness to collaborate with other centers in order to rapidly translate discoveries in HF research to advances in the treatment of HF by performing small multi-center trials within the HF-CRN. In support of this application, we present two protocols that test novel therapeutic approaches for important HF populations which are based on our previous laboratory based, patient oriented and population based studies and require a multi-center, academic research network for completion. We will also provide an application for a Clinical Research Skills Development Core to facilitate the training of future clinical HF investigators. Four specific aims will be addressed. Specific Aim 1. Document that the Mayo HF Program has the clinical resources and research support infrastructure as well as the clinical, translational and basic research expertise to assist in the development of and to insure active collaborative participation in the HF-CRN. Specific Aim 2. Protocol 1: A randomized, double-blind, prospective treatment trial of chronic subcutaneous (SQ) brain natriuretic peptide (BNP) in patients with clinical heart failure and preserved ejection fraction (referred to subsequently as diastolic heart failure, DHF). The hypothesis is that compared to standard therapy, therapy with chronic SQ BNP will improve clinical status by altering the key pathophysiological domains that characterize clinical HF in patients with DHF. Specific Aim 3. Protocol 2: A randomized, placebo controlled study of low dose brain natriuretic peptide (BNP) infusion without or with concomitant phosphodiesterase V inhibition (sildenafil) versus standard therapy in patients at high risk for worsening renal function (cardiorenal syndrome, CRS) during treatment of acute decompensated HF (ADHF). The hypotheses are 1) compared to standard therapy, low dose BNP will improve renal function in patients with ADHF at high risk for the CRS;and 2) compared to standard therapy or low dose BNP alone, combination therapy with low dose BNP and phosphodiesterase V inhibition will improve renal function in patients with ADHF at high risk for the CRS. Specific Aim 4. Establish a Clinical HF Research Skills Development Core The objective is to train future investigators in clinical HF research facilitating their ability to attain independent status. (End of Abstract)